Whole genome sequencing is a specialized function requiring expertise, special instruments and facilities along with informatics capabilities. This function cannot be performed in individual laboratories. Whole genome sequencing is also evolving rapidly and constantly improving the read capabilities, number of samples per run and informatics capabilities. There is only limited number of facilities available worldwide with such capabilities. Welcome Trust Sanger Institute (WTSI) is a leader in sequencing the human genome, contributing one third of all the sequences and has made numerous contributions to other large genomes, Idad efforts to sequence pathogens and disease vectors and mouse Rl strain genomes. WTSI is committed to continually appraising new sequencing technologies, using in-house testing wherever possible, and will use whatever future technology is most suitable and cost-effective for the applications demanded by the science pursued at the Institute. The purpose of Core D is to provide for comprehensive genomic sequence analyses by utilizing a state of the art 'next generation' sequencing platform for both the sequencing of all coding exons/miRNA genes and the identification and characterization of genome-wide rearrangements at base-pair resolution in samples detailed in Projects 1 and 2. To meet these goals, in Core D we will pursue the following specific aims: to generate comprehensive somatic mutation data for all coding exons and miRNA genes from selected samples from patients progressing from monoclonal gammopathy of underemined significance (MGUS) smoldering multiple myeloma (SMM) to active multiple myeloma (MM) or MM evolution from diagnosis to relapse (Specific Aim 1); and to generate a genome-wide rean^angement data at base-pair resolution from selected samples to explore genomic changes during MM evolution from diagnosis to relapse (Specific Aim 2). Further, the core will provide bioinformatics expertise in the management and analysis of data produced within the core to support the projects.